The compound 2-phenyl-1,3-propanediol (PPD) is a key intermediate in the synthesis of the anti-epileptic drug felbamate. The current commercial preparation of PPD utilizes essentially the same procedure as disclosed in U.S. Pat. No. 4,868,327, which comprises hydrogenolysis of 2-phenyl-2-nitro-1,3-propanediol (I). In the current process, the hydrogenolysis is carried out in MeOH using palladium on CaCO.sub.3 as a catalyst, with PdO on CaCO.sub.3 giving the best results for commercial scale production. ##STR3##
The current process suffers from several problems which are severely exacerbated when the process is utilized for commercial scale production of PPD. These problems include: (a) the necessity of very high solvent volumes for consistent results [.gtoreq.10 volumes of MeOH based on the amount of compound (I)]; (b) the need to use PdO on CaCO.sub.3, an expensive and difficult to recover catalyst, for optimal performance; (c) a slow rate of reaction with total reaction time being unpredictable and ranging from 20 to 40 hours; (d) a high sensitivity to temperature, with unacceptably slow reaction rates occurring below 25.degree. C. and a build up in the level of impurities at reaction temperatures over 25.degree. C.; and (e) the necessity of frequently venting gaseous by-products of the reaction (typically every 3 h). In addition, the current process is extremely sensitive to other variables, such as the purity of starting material, i.e., compound (I), the quality of the palladium catalyst, the type of reaction vessel used (e.g. the reaction is generally more consistent in glass lined reactors as compared to stainless steel vessels), and the manner in which by-product gases are vented.
The highly unpredictable nature of the current process is predominantly due to the formation of NH.sub.3 as a by-product gas during the hydrogenolysis of compound (I). Compound (I) is very sensitive to base, undergoing a base-catalyzed dehydroxymethylation side-reactions to form compounds (II) and (III), which then undergo hydrogenolysis to form a variety of impurities. In particular 2-phenylethanol is generally formed as an impurity during the current process, with levels of this impurity as high as 15%. ##STR4##